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...include fetal risk from receiving leflunomide and exposure to tumor necrosis factor in pregnancy; timing and management of lupus nephritis in pregnancy, and asymptomatic elevated antiphospholipid antibodies.
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Should women discontinue medications for rheumatoid arthritis (RA) when pregnant? Should they become pregnant with previous lupus nephritis? Should they risk miscarriage with positive anti-phospholipid (aPL) antibodies?
Pregnant women with rheumatologic disease often face dilemmas created by their pregnancy and are at increased risk for both pregnancy--and disease-related complications. In this article, I present several cases of women who had a rheumatologic disease and were pregnant or wanted to be and offer advice and recommendations for addressing their dilemmas.
Dilemma 1: Pregnancy in a woman receiving leflunomide and etanercept for RA
A 28-year-old white woman with a 5-year history of RA calls on a Monday morning because she dis covered that she is pregnant, probably about 8 weeks gestation, based on her last menstrual period. She has been taking leflunomide, 20 mg/d, plus etanercept, 50 mg1wk, for the past 2 years and has been doing well on this regimen. She asks whether she should continue her medications and, if she does, what effect they will have on her baby.
Comments. Any woman of reproductive age should be instructed not to become pregnant while taking leflunomide or methotrexate (MTX). Both medications are FDA category X (Table 1), meaning that the high potential of harm to the developing fetus outweighs any potential benefit of the drug to the mother. Leflunomide inhibits purine metabolism, interfering with DNA formation and leading to chromosome abnormalities and cell death. MTX is a dihydrofolate reductase inhibitor that decreases maternal folic acid reserves; having low folic acid levels early in pregnancy increases the risk of neural tube defects.
With first trimester exposure, in particular, the effects of leflunomide and MTX can be devastating to a fetus. The most common birth defects among women exposed to these medications are abnormalities in the CNS, limbs, and palate, as well as cranial ossification. (1) MTX often is used to abort ectopic pregnancies but in doses several times higher than typically used to manage rheumatologic disease.
The manufacturers of leflunomide and MTX recommend that these drugs be discontinued at least 3 months before conception is attempted, because both drugs have prolonged half-lives. Women planning pregnancy should take at least 1 mg of folic acid per day, although more may be prudent to ensure that stores are replenished.
If a woman has taken leflunomide within 2 years of conception, obtaining a serum leflunomide level is recommended. If the level is above 0.02 mg/L, then a course of cholestyramine is recommended to hasten clearance of the drug; 8 g of cholestyramine is administered as a drink in juice or water 3 times a day for 11 days. Taking this medication is not pleasant, but it is adequately tolerated in motivated patients.
If a pregnancy is discovered in a woman taking leflunomide, the drug should be stopped and a course of cholestyramine started immediately. There is no specific treatment available for women who conceive while taking MTX, although treatment with higher doses of folic acid is advisable.
In spite of dire warnings, not all fetuses exposed to leflunomide or MTX will be...
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